Haemophilus influenzae type b is the leading cause of bacterial meningitis in infants and children and a major cause of septicemia, septic arthritis pneumonia and epiglottitis. Pneumococcus type 6A is a major cause of otitis media and the most frequent pneumococcal type causing meningitis and pneumonia. Anticapsular antibodies are protective; their induction by purified capsular polysaccharide is hampered by both their poor immunogenicity in the young age group and lack of anamestic response. In contrast, conjugates composed of these polysaccharides covalently bound to tetanus toxoid were immunogenic in laboratory mice and infant rhesus; this response could be boosted by further injections. Simultaneous injections of both cojugates with tetanus toxoid or with DTP enhanced the response to both polysaccharides. Adult volunteers were immunized 2 times at 3 week intervals with conjugates composed of H. influenzae type b, the closely related E. coli K100 or Pn6A polysaccharides and tetanus toxoid in the following schedule: Group 1: Hib-TT, 50 Mug/dose; Group 2: Pn6A TT, 50 Mug/dose; Group 3: Hib-TT, 50 Mug + Pn6A TT, 50 Mug; Group 4: Hib-TT, 50 Mug + K100-TT, 50 Mug; Group 5: Hib-TT, 100 Mug. Local and systemic reactions were noted in about half of the vaccinees following the first immunization, especially in the groups that received the 100 Mug dose. No serious reactions occurred. 50 Mug Hib TT alone was given to grops 3, 4, and 5 for the 2nd immunization. The antibody responses, assayed by RIA and ELISA, showed marked increases in antibody levles in greater than 95% of the volunteers. Hib antibodies increased 180 fold, Pn6A: 7 fold, and TT 10-20 fold. A maximal response occurred in most volunteers after the 1st injection, with no booster response after the 2nd. No relation was found between the preimmune levels to the vaccine components or the rate of antibody rise to the side effects of the vaccines. The isotype and biological activities of the conjugate-induced Hib antibodies have been analyzed and compared to those induced by the polysaccharide alone.